Based On HSG Regulation Of Wnt/?-catenin Pathway And Its Correlation With COPD TCM Syndromes

Objective:The correlation analysis of COPD patients'TCM syndrome with ?-catenin gene, try to explore TCM syndrome diagnosis of COPD from the genetic level.Animal experiments to explore the relationship between HSG and Wnt/ ?-catenin signal transduction pathway in airway remodeling in COPD, try to elaborate HSG gene regulation mechanism of airway remodeling.The methods:61 COPD in-hospital patients selected for the study,while 20 cases selected for the experimental control group of normal. The TCM syndrome of patients were differentiated and classified based on "Traditional Chinese Internal Medicine", in which 21 people in syndrome of turbid phlegm obstructing lung group,17 people in syndrome of phlegm-heat obstructing lung,23 people in syndrome of qi deficiency of lung and kidney. All staff collected venous blood and Realtime-PCR analysis of ?-catein in blood. COPD patients continued to do the pulmonary function tests and arterial blood gas analysis, filled in the CAT and mMRC questionnaire mMRC at the same time. The physician assessing the patient's condition according to the "Chronic obstructive pulmonary disease treatment guidelines(2013 Revision).100 healthy male SD rats were divided into normal control group and COPD model group. COPD model group were intratracheal injection of lipopolysaccharide plus smoked methods.Used hematoxylin-eosin staining, immunohistochemical stain to identify COPD model and observed the changes of ?-catenin protein expression in two groups. Cultured the rat airway primary fibroblasts cells in vitro by tissue blocking adhering method. Realtime-PCR were used to detect the HSG and ?-catenin mRNA expression in fibroblasts. Used Western blotting assay and ELISA for HSG? ?-catenin?GSK-3??TGF-?1?MMP-9 in small airway fibroblasts. Eventually, explored the correlation analysis of HSG,?-catenin with TGF-?1?MMP-9.Statistics:Data were statistically analyzed using SPSS16.0 software. Count data were compared using the Chi-Square test. The measurement date in line with normal distribution used ANOVA, while measurement data did not meet the normal distribution using the Wilcoxon test. The mean for diverse comparion, data were consistent with homogeneity of variance to use LSD test, while to use Dunnett's T3 test. Used completely random t test between the two group compared. Used Pearson product moment correlation coefficient or Spearman correlation coefficients describing conducted bivariate correlation analysis.Results:Clinical trials1. Normal control group blood ?-catenin gene expression was lower than various TCM Syndrome, there was a significant difference(P<0.01).2. In COPD TCM syndrome from syndrome of turbid phlegm obstructing lung ?syndrome of phlegm-heat obstructing lung?syndrome of qi deficiency of lung and kidney,?-catenin gene expression gradually increased in blood. syndrome of qi deficiency of lung and kidney group compared with syndrome of turbid phlegm obstructing lung group (P<0.01). syndrome of qi deficiency of lung and kidney group compared with syndrome of phlegm-heat obstructing lung group. there was no statistical significance between syndrome of turbid phlegm obstructing lung group and syndrome of phlegm-heat obstructing lung group.3.There was statistical significance between A group and D group(P<0.05).Animal experiment1. COPD model group airway fibroblasts HSG mRNA, protein expression were lower than the normal group.2. COPD airway fibroblasts Wnt/?-catenin signaling pathway mRKA, protein expression of ?-catenin key genes were higher than normal group. Expression of P-GSK-3?was also higher than the normal group. The signaling pathways downstream gene TGF-?1, MMP-9 expression were also high compared with the normal group.3. IHC confirmed the ?-catenin nuclear translocation in COPD airway fibroblasts, in which Wnt/beta-catenin signaling pathway was abnormally activated.4. HSG mRNA expression and mRNA expression of ?-catenin and TGF-?1, MMP-9 secretion of both cytokines were negatively correlated.Conclusions:1.The expression of ?-catenin gene in the blood could be used as objective reference index to distinguish type of COPD TCM.2. There was a correlation between ?-catenin gene expression and COPD progression.3. The Wnt/?-catenin signaling pathway was abnormally activated in COPD airway fibroblasts.4. The HSG gene might regulated Wnt/?-catenin signaling pathway, whcih resulted in inhibiting the fibroblasts proliferation.